Bioorthogonal micellar nanoreactors for prodrug cancer therapy using an inverse-electron-demand Diels-Alder reaction.

Block copolymer micelles functionalized with tetrazine groups can act as nanoreactors to activate a trans -cyclooctene-functionalized prodrug for releasing anticancer drugs via a bioorthogonal inverse-electron-demand Diels-Alder (IEDDA) reaction. In addition, the IEDDA reaction can be accelerated in the micellar nanoreactor system compared to the free tetrazine system. Moreover, In vivo prodrug activation in a mouse tumor model led to the inhibition of tumor growth without significant systemic toxicity. These results demonstrated their potential for applications as bioorthogonal micellar nanoreactors for cancer chemotherapy.